This revised Digestive Diseases Research Core Center proposal will unite investigators from multiple discipline to achieve a new level of integration in digestive biology, pathobiology, and therapy. The scientific focus is on the molecular controls of cellular growth and differentiation in digestive organs and on the relationship of these processes to inflammatory and neoplastic diseases. The research base was refined by a process of discussion, exchanges of reagents, and scientific collaborations between investigators. The number of investigators was decreased from 35 in the initial proposal to 26 scientists who want to further develop an interactive research group. Within the scientific focus, a number of themes have evolved which link Center investigators together, including gene regulation, inflammation and immunology, and regulation of cell growth and tumor biology. Four scientific Cores have been developed with the goals of providing digestive-specific services and reagents and stimulating collaborative research. The cores include Morphology, Molecular Biology, Transgenic and Chimeric Mouse, and Vector. An administrative Core will be led by the Director, Peter G. Traber, and the Scientific/Associate Director, Rebecca A. Traub. This Core will direct the financial and organizational aspects of the center, including development of an enrichment program and electronic communications. Pilot/Feasibility Projects were selected based on their relevance to the scientific focus and the priority of promoting digestive research among young investigators. The proposals include: 1) positional cloning of the gene responsible for the Alagille Syndrome, 2) PRL-1 in intestinal development, 3) induction and patterning of endodermal lineages in Xenopus laevis, and 4) response syndrome. In addition to the Principal Investigators of these proposals, there is a cadre of outstanding young investigators who will benefit from a Digestive Diseases Center at University of Pennsylvania. In summary, this revised proposal provides evidence that the nascent Center proposed two years ago has matured and developed into an entity within the University scientific community. The University of Pennsylvania is poised to take excellent advantage of funding for a Digestive Disease Research Core Center.